Sodium fluoride (NaF) in the form of mouthwashes, toothpaste, fluoridated water, and tablets was used for the protection from caries Aims: to study some serum biochemical changes of liver and kidney. Materials and Methods: Twelve healthy male rabbits were involved. Control group: six rabbits were kept on a standard diet and water with no any treatment. Treatment group: another six rabbits were treated by NaF at the dose of 20 mg/kg/day dissolved in 400 ml of distill water. At the end of 30 days of treatment, five ml of blood samples were taken from each animal during an animal sacrifice. Serum analysis was done by colorimetric Assay kit for total antioxidant capacity(TAC), Malondialdehyde (MDA), alkaline phosphatase (ALP), Aminotransferases (AST and ALT), Creatinine and urea. Results: there were significant differences between the control and treatment groups. Significant reduction in TAOC with a significant increase in MDA, ALP, AST, ALT, creatinine, and urea in the treatment group compared to the control group. Conclusion: (NaF) at the dose of 20 mg/kg/day for 30 days can result in a significant change in serum biochemical markers of liver and kidney in rabbits.